Dissecting the Interaction of FGF8 with Receptor FGFRL1.

Zhuang, Lei; Vogel, Monique; Villiger, Peter M.; Trueb, Beat (2020). Dissecting the Interaction of FGF8 with Receptor FGFRL1. Biomolecules, 10(10) MDPI 10.3390/biom10101399

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In mammals, the novel protein fibroblast growth factor receptor-like 1 (FGFRL1) is involved in the development of metanephric kidneys. It appears that this receptor controls a crucial transition of the induced metanephric mesenchyme to epithelial renal vesicles, which further develop into functional nephrons. FGFRL1 knockout mice lack metanephric kidneys and do not express any fibroblast growth factor (FGF) 8 in the metanephric mesenchyme, suggesting that FGFRL1 and FGF8 play a decisive role during kidney formation. FGFRL1 consists of three extracellular immunoglobulin (Ig) domains (Ig1-Ig2-Ig3), a transmembrane domain and a short intracellular domain. We have prepared the extracellular domain (Ig123), the three individual Ig domains (Ig1, Ig2, Ig3) as well as all combinations containing two Ig domains (Ig12, Ig23, Ig13) in recombinant form in human cells. All polypeptides that contain the Ig2 domain (Ig123, Ig12, Ig23, Ig2) were found to interact with FGF8 with very high affinity, whereas all constructs that lack the Ig2 domain (Ig1, Ig3, Ig13) poorly interacted with FGF8 as shown by ELISA and surface plasmon resonance. It is therefore likely that FGFRL1 represents a physiological receptor for FGF8 in the kidney and that the ligand primarily binds to the Ig2 domain of the receptor. With Biacore experiments, we also measured the affinity of FGF8 for the different constructs. All constructs containing the Ig2 domain showed a rapid association and a slow dissociation phase, from which a KD of 2-3 × 10-9 M was calculated. Our data support the hypothesis that binding of FGF8 to FGFRL1 could play an important role in driving the formation of nephrons in the developing kidney.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie

UniBE Contributor:

Zhuang, Lei; Vogel, Monique; Villiger, Peter and Trueb, Beat

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2218-273X

Publisher:

MDPI

Language:

English

Submitter:

Lee-Anne Brand

Date Deposited:

20 Oct 2020 16:48

Last Modified:

25 Oct 2020 02:15

Publisher DOI:

10.3390/biom10101399

PubMed ID:

33019532

Uncontrolled Keywords:

FGF8 FGFRL1 fibroblast growth factor (FGF) fibroblast growth factor receptor (FGFR) kidney development mesenchymal-to-epithelial transition (MET)

BORIS DOI:

10.7892/boris.146998

URI:

https://boris.unibe.ch/id/eprint/146998

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